scholarly journals The orally active renin inhibitor SPP100 blocks the renin-angiotensin system in humans equally well as enalapril

2001 ◽  
Vol 14 (11) ◽  
pp. A17 ◽  
Author(s):  
J Nussberger
Keyword(s):  
Renin Angiotensin System ◽  
Renin Inhibitor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin ◽  
Orally Active

scholarly journals Aliskiren –An overview

2015 ◽  
Vol 25 (1) ◽  
pp. 21-24
Author(s):  
NS Neki
Keyword(s):  
Target Organ Damage ◽  
Effective Means ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Renin Inhibitor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
New Class ◽  
Direct Renin Inhibitor ◽  
Orally Active

The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system (RAAS) is a major endocrine/ paracrine system that regulates blood pressure (BP) via angiotensin release as well as fluid and electrolyte homeostasis via aldosterone release. RAAS should be constantly suppressed and any degree of activity may lead to hypertension (HTN) and associated target organ damage. Activation of the RAAS in the pathogenesis of hypertension, cardiovascular disease(CVD) and renal disease is well documented. Also benefits of inhibition of RAAS, as an effective way to intervene in the pathogenesis of HTN, CVD and chronic renal failure(CRF) has been well recognized. Inhibition of renin activity and the blockage of RAAS cascade at its primary steps, has long been proposed as the optimal means of RAAS inhibition. Renin inhibitor provides more effective means of RAAS Inhibition. Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight direct renin inhibitor (DRI) available for clinical use and potential new approach to the blockade of the RAAS.Bangladesh J Medicine Jan 2014; 25 (1) : 21-24

Active renin and angiotensinogen in cardiac interstitial fluid after myocardial infarction

1999 ◽  
Vol 276 (6) ◽  
pp. H1818-H1826 ◽  
Author(s):  
Alan T. Hirsch ◽  
John A. Opsahl ◽  
Mary M. Lunzer ◽  
Stephen A. Katz
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
Interstitial Fluid ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin

The renin-angiotensin system promotes cardiac hypertrophy after myocardial infarction. The purpose of this study was to measure renin and angiotensinogen in plasma and myocardium 10 days after myocardial infarction. Infarction involving 45 ± 4% of left ventricular circumference with accompanying hypertrophy was induced in rats ( n = 14). Plasma and myocardial renin were increased after infarction compared with sham controls ( n = 8) (27.4 ± 3.2 vs. 7.5 ± 1.8 ng ANG I ⋅ ml plasma ⋅ h−1, P < 0.0002; and 8.8 ± 1.6 vs. 2.5 ± 0.1 ng ANG I ⋅ g myocardium−1 ⋅ h−1, P < 0.008, respectively). After infarction, myocardial renin was correlated with infarct size ( r = 0.62, P < 0.02) and plasma renin ( r = 0.55, P < 0.04). Plasma angiotensinogen decreased in infarct animals, but myocardial angiotensinogen was not different from shams (1.1 ± 0.08 vs. 2.03 ± 0.06 nM/ml plasma, P < 0.002; and 0.081 ± 0.008 vs. 0.070 ± 0.004 nM/g myocardium, respectively). In conclusion, myocardial renin increased after infarction in proportion to plasma renin and infarct size, and myocardial angiotensinogen was maintained after infarction despite decreased plasma angiotensinogen and increased levels of myocardial renin.

Renin-angiotensin system: oral contraception and exercise in healthy female subjects

1985 ◽  
Vol 59 (6) ◽  
pp. 1690-1697 ◽  
Author(s):  
I. A. Huisveld ◽  
F. M. Derkx ◽  
B. N. Bouma ◽  
W. B. Erich ◽  
M. A. Schalekamp
Keyword(s):  
Oral Contraceptives ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Oral Contraception ◽  
Renin Substrate ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin ◽  
Healthy Female ◽  
Female Subjects

The effect of oral contraception and of exercise on the renin-angiotensin system was studied in 20 highly trained athletes, of whom 10 were ingesting oral contraceptives (users) and 10 were not (nonusers), and in 24 sedentary age-matched healthy female subjects, of whom 13 were users and 11 were nonusers. No training-related effects were observed with the exception of renin substrate, which was significantly higher in the athletes. The plasma concentrations of active renin and of trypsin-activatable prorenin were significantly lower in the subjects taking oral contraceptives. Renin substrate, however, was significantly higher in the oral contraceptives group. No difference in plasma renin activity (PRA) was observed between users and nonusers. The results demonstrate the well-known estrogen-induced stimulation of renin substrate synthesis by the liver and suggest a decreased secretion of renin by the kidney. Exhaustive exercise of short duration, performed by the trained athletes only, stimulated the renin-angiotensin system. An increase in PRA and in active renin concentration was observed. The prorenin concentration did not change significantly. The magnitude of the exercise-induced changes was considerably influenced by oral contraceptive medication. Nonusers showed a significantly greater increase in PRA and active renin and total renin concentration than users. Renin substrate decreased significantly during exercise in the nonusers only. These results demonstrate that oral contraceptives have a suppressive effect on renin secretion at rest, an effect that becomes more prominent during exercise, i.e., physiological stimulation.

scholarly journals Effect of captopril on the release of the components of the renin-angiotensin system into plasma and lymph.

1992 ◽  
Vol 2 (7) ◽  
pp. 1241-1250 ◽  
Author(s):  
C S Wilcox ◽  
V J Dzau
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Lymph ◽  
Active Renin ◽  
Renal Interstitium ◽  
Arterial Plasma ◽  
Renal Vascular ◽  
Venous Plasma

The effects of captopril on the intrarenal renin-angiotensin system were assessed from measurements in arterial plasma, renal venous plasma, and renal lymph from salt-depleted dogs. In the basal state, immunoreactive angiotensin II (Ang II) in renal venous plasma averaged only 60 +/- 12% (P less than 0.01) of arterial plasma, although the concentration of Ang II in renal lymph was 2.0 +/- 0.4-fold (P less than 0.05) greater. The Ang II concentration of renal lymph incubated ex vivo at 37 degrees C doubled in 10 to 15 min, which was the time taken to collect renal lymph samples. Compared with arterial plasma, renal lymph contained lower concentrations (P less than 0.01) of renin substrate and angiotensin-converting enzyme but higher concentrations of active (5.3 +/- 2.1-fold) and inactive (8.9 +/- 3.2-fold) renin. Although captopril increased the secretion of active renin into renal venous plasma by six-fold, the secretion of total renin was unchanged because of a reciprocal fall in the secretion of inactive renin. The percent reduction in renal vascular resistance with captopril correlated with the percent fall in Ang II in renal lymph (r = 0.70). In conclusion: (1) all components of the renin-angiotensin system are represented in the renal interstitium, as reflected in lymph; (2) Ang II concentrations in renal lymph in vivo approximate arterial levels; (3) increased secretion of active renin into plasma during intrarenal infusion of captopril into denervated kidneys is due predominantly to renin activation; and (4) renal vascular resistance may depend on the concentration of Ang II in the renal interstitium.

Abstract 020: A Mitochondrial Renin-Angiotensin System: Internalization of Angiotensinogen

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Bryan A Wilson ◽  
Nancy T Pirro ◽  
TanYa M Gwathmey ◽  
James C Rose ◽  
Mark C Chappell
Keyword(s):  
Renin Angiotensin System ◽  
Anion Channel ◽  
Protein Band ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Voltage Dependent Anion Channel ◽  
Cell Organelles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin

There is compelling evidence for actions of an intracellular renin-angiotensin system (RAS) in various cell organelles including the endoplasmic reticulum, nucleus and the mitochondria (Mito). Indeed, angiotensin (Ang) AT1 and AT2 receptor subtypes were functionally linked to Mito respiration and nitric oxide production, respectively in a previous study. Since elucidation of mitochondrial pathways for expression of RAS protein components as well as Ang II or Ang-(1-7) is equivocal at this time, we undertook a biochemical analysis of the Mito RAS from adult male sheep kidney. Cortical Mito were isolated by differential centrifugation and a discontinuous Percoll gradient. Purified Mito were co-enriched in the voltage-dependent anion channel, an outer Mito membrane marker as well as ATP synthase, an inner membrane marker. Angiotensinogen (Aogen; 55 kDa) was detected in Mito extracts by an Aogen antibody to an internal sequence of the protein, but not with an antibody directed against the Ang I N-terminus. Two different renin antibodies identified a major 35 kDa protein band in the isolated Mito. Using the Ang I-directed Aogen antibody, active renin was confirmed by hydrolysis of Aogen that was abolished by aliskiren; however, trypsin exposure did not increase renin activity in the Mito. A pro-renin receptor (PRR) antibody failed to identify proteins in three Mito preparations, but revealed a prominent band in renal cortical membranes that corresponds to the size of PRR. Angiotensin peptides were quantified by three direct RIAs; the Mito content of Ang II and Ang-(1-7) were higher as compared to Ang I [23 ± 8 and 58 ± 17 vs. 2 ± 1 fmol/mg protein; p<0.01, n=3]. Additionally, both neprilysin and thimet oligopeptidase activities that processed Ang I to Ang-(1-7) were evident. Finally, cortical Mito internalized radiolabeled Aogen at a rate of 33 ± 9 fmol/min/mg protein (n=3) at 37°C. The subsequent analysis of the labeled Mito by SDS-gel fractionation revealed a predominant radioactive band of 55 kDa for Aogen. Collectively, our data suggest that the internalization of Aogen and subsequent processing by active renin may yield des-[Ang I]-Aogen and the active peptides Ang II and Ang-(1-7) that may potentially contribute to mitochondrial function within the kidney.

Sign in / Sign up

Export Citation Format

Share Document